AACR 2025 Poster 7335

Comparison of ADCC-Mediated Efficacy of CLDN18.2 mAb Zolbetuximab in hCD16A - CB17SCID HuGEMM Mice and CB17SCID Mice Bearing the SUN-6011 Tumor Model

Lily Rong Wang, Sylvia Xiaoze Wang, Kaixia Lian, Rongfei Lu, Haijuan Yu, Jie Lin, Ludovic Bourre, Jessie JingJing Wang

The mechanisms of action of cytotoxic monoclonal antibodies (mAbs) include FcγR-dependent mechanisms to induce antibody-dependent cell cytotoxicity (ADCC). In mice, ADCC relies on mFcγRIII expressed on NK cells, while human NK cells depend on hFcγRIIIA (hCD16A). hFcγRIIIA (CD16A) and mFcγRIII (mCD16) are also expressed on monocytes/macrophages from human or mice, respectively. Additionally, the mouse homologous gene of hFcγRIIIA is mFcγRIV (mCD16-2); however, mFcγRIV is not expressed on mouse NK cells.

Human IgG1 display significant affinity differences between mouse and human FcγRs, which can impact their efficacy in preclinical models. Additionally, testing an affinity-enhanced Fc-engineered antibody in a mouse without the human FcγR counterparts provides limited predictive value. Therefore, preclinical mouse models expressing human FcγRs are essential to evaluate the clinical Fc potent antibody.

Download this Poster to Discover:

• The importance of preclinical models that express human antigens for immunotherapy research
  
  
• A hCD16A-CB17SCID humanized genetically modified mouse model for the evaluation of immunotherapies
  
  
• How to evaluate ADCC function in a relevant translational model

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